Introduction: Acute onset of severe psychiatric symptoms or regression may occur in children with premorbid neurodevelopmental disorders, although typically developing children can also be affected. Infections or other stressors are likely triggers. The underlying causes are unclear, but a current hypothesis suggests the convergence of genes that influence neuronal and immunological function.
View Article and Find Full Text PDFExcess adiposity is at the root of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as first-line treatments for T2D based on significant weight loss results. The composition of weight loss using most diets consists of <25% fat-free mass (FFM) loss, with the remainder from fat stores.
View Article and Find Full Text PDFBackground: Biological age may be estimated by proteomic aging clocks (PACs). Previous published PACs were constructed either in smaller studies or mainly in white individuals, and they used proteomic measures from only one-time point. In this study, we created de novo PACs and compared their performance to published PACs at 2 different time points in the Atherosclerosis Risk in Communities (ARIC) study of white and black participants (around 75% white and 25% black).
View Article and Find Full Text PDFBackground And Aims: Incident heart failure (HF) among individuals with chronic kidney disease (CKD) incurs hospitalizations that burden patients and health care systems. There are few preventative therapies, and the Pooled Cohort equations to Prevent Heart Failure (PCP-HF) perform poorly in the setting of CKD. New drug targets and better risk stratification are urgently needed.
View Article and Find Full Text PDFKey Points: Integrated analysis of proteome and metabolome identifies modules associated with CKD progression and kidney failure. Ephrin transmembrane proteins and podocyte-expressed CRIM1 and NPNT emerged as central components and warrant experimental and clinical investigation.
Background: Proteins and metabolites play crucial roles in various biological functions and are frequently interconnected through enzymatic or transport processes.
Background: Previous studies have determined that up to 6% of patients with aspirin-exacerbated respiratory disease (AERD) have family history of AERD, indicating a possible link with genetic polymorphisms. However, whole exome sequencing (WES) studies of such associations are currently lacking.
Objectives: We sought to examine whether WES can identify pathogenic variants associated with AERD.
Background: Patients with kidney failure suffer high mortality, and we currently lack markers for risk stratification for these patients. We carried out a quality control study of a modified aptamer assay (SomaScan v.4.
View Article and Find Full Text PDFPurpose: The purpose of this study was to assess the feasibility of hospital-wide implementation of an above-cuff vocalization (ACV) protocol using ACV-capable tracheostomy tubes and its impact on patient speech in four intensive care unit (ICU) patient populations.
Method: This research was an observational pre-post study that was conducted over a 26-month period and included 323 critically ill adult ICU patients who underwent tracheostomy in a 365-bed academic tertiary care hospital. ACV was assessed using a protocol developed by a multidisciplinary team.
Aim: To investigate the effects of an orlistat mouth rinse on the intake of a high-fat meal.
Methods: A double-blind, balanced order, crossover study was conducted in participants (n = 10, body mass index 25-30 kg/m ) assigned to receive placebo or orlistat (24 mg/mL) prior to a high-fat meal. Participants were divided into low- or high-fat consumers based on calories consumed from fat following placebo administration.
Background: Single-cell technologies to analyze transcription and chromatin structure have been widely used in many research areas to reveal the functions and molecular properties of cells at single-cell resolution. Sample multiplexing techniques are valuable when performing single-cell analysis, reducing technical variation and permitting cost efficiencies. Several commercially available methods have been used in many scRNA-seq studies.
View Article and Find Full Text PDFUnlabelled: New Western-style diet 1 (NWD1), a purified diet establishing mouse exposure to key nutrients recapitulating levels that increase human risk for intestinal cancer, reproducibly causes mouse sporadic intestinal and colonic tumors reflecting human etiology, incidence, frequency, and lag with developmental age. Complex NWD1 stem cell and lineage reprogramming was deconvolved by bulk and single-cell RNA sequencing, single-cell Assay for Transposase-Accessible Chromatin using sequencing, functional genomics, and imaging. NWD1 extensively, rapidly, and reversibly, reprogrammed Lgr5hi stem cells, epigenetically downregulating Ppargc1a expression, altering mitochondrial structure and function.
View Article and Find Full Text PDFAims: Chronic kidney disease (CKD) is widely prevalent and independently increases cardiovascular risk. Cardiovascular risk prediction tools derived in the general population perform poorly in CKD. Through large-scale proteomics discovery, this study aimed to create more accurate cardiovascular risk models.
View Article and Find Full Text PDFSignificance Statement: We describe circulating proteins associated with albuminuria in a population of African American Study of Kidney Disease and Hypertension with CKD (AASK) using the largest proteomic platform to date: nearly 7000 circulating proteins, representing approximately 2000 new targets. Findings were replicated in a subset of a general population cohort with kidney disease (ARIC) and a population with CKD Chronic Renal Insufficiency Cohort (CRIC). In cross-sectional analysis, 104 proteins were significantly associated with albuminuria in the Black group, of which 67 of 77 available proteins were replicated in ARIC and 68 of 71 available proteins in CRIC.
View Article and Find Full Text PDFMyelodysplastic syndrome (MDS) is a clonal malignancy arising in hematopoietic stem cells (HSCs). The mechanisms of MDS initiation in HSCs are still poorly understood. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is frequently activated in acute myeloid leukemia, but in MDS, PI3K/AKT is often down-regulated.
View Article and Find Full Text PDFBackground: We carried out a study of the aptamer proteomic assay, SomaScan V4, to evaluate the analytical and biological variability of the assay in plasma samples of patients with moderate to severe chronic kidney disease (CKD).
Methods: Plasma samples were selected from 2 sources: (a) 24 participants from the Chronic Renal Insufficiency Cohort (CRIC) and (b) 49 patients from the Brigham and Women's Hospital-Kidney/Renal Clinic. We calculated intra-assay variability from both sources and examined short-term biological variability in samples from the Brigham clinic.
Background: Testican-2 was recently identified as a podocyte-derived protein that is released into circulation by the kidneys and is positively correlated with eGFR and eGFR slope. However, whether higher testican-2 levels are associated with lower risk of ESKD is unknown.
Methods: Aptamer-based proteomics assessed blood testican-2 levels among participants in the African American Study of Kidney Disease and Hypertension (AASK, n =703), the Chronic Renal Insufficiency Cohort (CRIC) study ( n =3196), and the Atherosclerosis Risk in Communities (ARIC) study ( n =4378).
Cell Mol Gastroenterol Hepatol
August 2022
Background And Aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs.
View Article and Find Full Text PDFIntroduction: We lack cardiovascular (CV) markers for patients with end-stage renal disease (ESRD), and left atrial (LA) strain has not been studied definitively in this population. We examined associations of LA reservoir, conduit, and booster strain with major adverse cardiovascular events (MACE) among stable patients with ESRD on dialysis.
Methods: One hundred and ninety patients in the Cardiac, Endothelial and Arterial Stiffness in ESRD study underwent echocardiography, including strain imaging.
Objective: To gather and evaluate veterinarians' perspectives about the impacts of the COVID-19 pandemic on the use of veterinary telehealth and on cat owners' versus dog owners' attitudes toward transmission of the SARS-CoV-2 virus from their pets.
Sample: 93 respondent veterinarians (47 in primary care practice and 46 in specialty practice).
Procedures: An online survey was conducted between June 15 and July 15, 2020, and included 21 questions concerning demographics, use of telehealth before and after the onset of the pandemic (before March 15, 2020, and between March 15 and June 15, 2020, respectively), changes in caseloads, and perception of clients' concerns about potential for transmission of the SARS-CoV-2 virus from pets.
Background: A better understanding of the pathophysiology involving coronary artery calcification (CAC) in patients on hemodialysis (HD) will help to develop new therapies. We sought to identify the differences in metabolomics profiles between patients on HD with and without CAC.
Methods: In this case-control study, nested within a cohort of 568 incident patients on HD, the cases were patients without diabetes with a CAC score >100 (=51), and controls were patients without diabetes with a CAC score of zero (=48).
J Am Soc Nephrol
September 2021
Background: Proteomic profiling may allow identification of plasma proteins that associate with subsequent changesin kidney function, elucidating biologic processes underlying the development and progression of CKD.
Methods: We quantified the association between 4877 plasma proteins and a composite outcome of ESKD or decline in eGFR by ≥50% among 9406 participants in the Atherosclerosis Risk in Communities (ARIC) Study (visit 3; mean age, 60 years) who were followed for a median of 14.4 years.